Enantioselective Formation Research Articles

ChemInform Abstract: Pd‐Catalyzed Desymmetric Intramolecular O‐Arylation Reaction: Enantioselective Synthesis of (3,4‐Dihydro‐2H‐chromen‐3‐yl)methanols.

An enantioselective intramolecular O-arylation was achieved through desymmetrization with Pd-catalyzed coupling reactions. The intramolecular asymmetric aryl C–O coupling reactions of 2-(2-haloaryl)propane-1,3-diols led to the enantioselective formation of chiral (3,4-dihydro-2H-chromen-3-yl)methanols in good yields and high enantiomeric selectivity.

ChemInform Abstract: Asymmetric Synthesis of Chiral Dihydrothiopyrans via an Organocatalytic Enantioselective Formal Thio [3 + 3] Cycloaddition Reaction with Binucleophilic Bisketone Thioethers.

AbstractAn unprecedented organocatalytic formal [3 + 3] cycloaddition process is described to yield 3,4‐dihydro‐2H‐thiopyrane derivatives from thiodiketones and cinnamic aldehydes.

Enzyme immobilised novel core-shell superparamagnetic nanocomposites for enantioselective formation of 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate.

Lipase immobilized novel high surface area core-shell superparamagnetic nanoparticles have been fabricated and used as efficient reusable catalysts for the selective production of pharmaceutically important chiral isomers from meso-cyclopent-2-en-1,4-diacetate.

Chiral fungicide triadimefon and triadimenol: Stereoselective transformation in greenhouse crops and soil, and toxicity to Daphnia magna

Various chiral pesticides are used in greenhouses to ensure high crop yields. However, detailed knowledge on the environmental behavior of such chiral contaminants with respect to enantioselectivity in the greenhouse has received little attention so far. Here, the widely used fungicide triadimefon was chosen as a “chiral probe” to investigate its enantioselective degradation and formation of triadimenol in greenhouse tomato, cucumber, and soil under different application modes. In addition, the stereoselectivity of individual isomers of triadimefon and triadimenol in aquatic toxicity were first studied. Significant differences in their acute toxicity to Daphnia magna were observed among the isomers. Under foliage application or soil irrigation application, S-(+)-triadimefon was preferentially degraded, resulting in relative enrichment of the more toxic R-(−)-enantiomer in tomato, cucumber, and soil. Further enantioselective analysis of converted triadimenol showed that the compositions of the four product stereoisomers were different and closely dependent on environmental conditions: the most toxic RS-(+)-triadimenol was the most preferentially produced isomer in tomato under foliage treatment, while the RR-(+)-triadimenol was proved to be the highest amount of metabolite isomer in cucumber and soil under both treatment modes and in tomato under soil treatment.

Pd-Catalyzed Desymmetric IntramolecularO-Arylation Reaction: Enantioselective Synthesis of (3,4-Dihydro-2H-chromen-3-yl)methanols

An enantioselective intramolecular O-arylation was achieved through desymmetrization with Pd-catalyzed coupling reactions. The intramolecular asymmetric aryl C-O coupling reactions of 2-(2-haloaryl)propane-1,3-diols led to the enantioselective formation of chiral (3,4-dihydro-2H-chromen-3-yl)methanols in good yields and high enantiomeric selectivity.

Asymmetric Synthesis of Chiral Dihydrothiopyrans via an Organocatalytic Enantioselective Formal Thio [3 + 3] Cycloaddition Reaction with Binucleophilic Bisketone Thioethers

An unprecedented organocatalytic highly enantioselective approach to a 3,4-dihydro-2H-thiopyran scaffold with two contiguous stereogenic centers has been implemented through a formal thio [3 + 3] cycloaddition process involving a Michael-aldol condensation cascade sequence. Notably, a new class of binucleophilic bisketone thioethers is designed for the process. Furthermore, the fine-tuning of their reactivity enables the cascade process to proceed with highly regioselectively.

Oxazoline‐Based Organocatalyst for Enantioselective Strecker Reactions: A Protocol for the Synthesis of Levamisole

A chiral oxazoline-based organocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N-benzhydrylimines with trimethylsilyl cyanide (TMSCN) as a cyanide source at -20 °C to give α-aminonitriles in high yield (96 %) with excellent chiral induction (up to 98 % ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organocatalyst in these reactions. The organocatalyst has been characterized by single-crystal X-ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.

Chemoenzymatic asymmetric synthesis of fluoxetine, atomoxetine, nisoxetine, and duloxetine

The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.

ChemInform Abstract: Enantioselective Formal Aza‐Diels—Alder Reactions of Enones with Cyclic Imines Catalyzed by Primary Aminothioureas.

AbstractA wide range of indolo‐ and benzoquinolizidine derivatives is prepared in high yields and diastereoselectivities.

A General Method for the Enantioselective Formation of Helical Nanofilaments

Homochirale helikale Nanofasern (HNFs) mit verdrillt-nematischer (TN-)Konfiguration sind nach einer allgemeinen Methode herstellbar. Durch Mischen gebogener Moleküle in der B4-Phase mit stabförmigen Molekülen in der nematischen Phase erhält man die Phasenabfolge N-Bx(B4/N). Homochirale HNFs in der Bx-Phase resultierten aus diesen Mischungen, wenn TN-Zellen abgekühlt wurden. Die homochiralen HNFs wurden rasterkraftmikroskopisch untersucht (siehe Bild).

A General Method for the Enantioselective Formation of Helical Nanofilaments

Controlling chirality: A general method to obtain homochiral helical nanofilaments (HNFs) based on a twisted nematic (TN) configuration was developed. By mixing bent-core molecules in the B4 phase with rod-like molecules in the nematic phase, the mixtures show the phase sequence of N–Bx(B4/N). Homochiral HNFs in the Bx phase were obtained from the mixtures when TN cells were cooled. The homochiral HNFs were observed by atomic force microscopy (see picture).

Catalytic Enantioconvergent Decarb­oxylative Allylic Alkylation of Allyl Indol­enin‐3‐carboxylates

AbstractA catalytic enantioconvergent process has been developed for the conversion of racemic allyl indolenin‐3‐carboxylates into enantiomerically enriched C3‐quaternary indolenines. A Pd‐catalyzed decarboxylative allylic alkylation reaction was employed for both stereoablation of the racemic allyl indolenin‐3‐carboxylates and enantioselective formation of the quaternary carbon center.

Stereoselectivity in the cytochrome P450-dependent N-demethylation and flavin monooxygenase-dependent N-oxidation of N,N-dimethylamphetamine

N,N-dimethylamphetamine (DMA), a methamphetamine (MA) analog, is known as a weak central nervous system stimulant. As DMA possesses a chiral center, we investigated the enantioselective formation of N,N-dimethylamphetamine N-oxide (DMANO) and MA from DMA using human liver microsomes, recombinant cytochrome P450 (CYP) 2D6, and flavin monooxygenases (FMO) 1 and 3. d-DMA was preferentially metabolized to MA, whereas l-DMA was more rapidly transformed to DMANO in human liver microsomes. CYP2D6 showed a preference for catalyzing N-demethylation of d-DMA, and the intrinsic clearance (Clint) ratio of d-isomer to l-isomer was 1.41. FMO1 catalyzed the formation of slightly less d-DMANO than l-DMANO, and the Clint ratio of the D- to L-isomer was 0.78. The reverse was observed for the formation of DMANO by FMO3. However, given the minor contribution of FMO3 compared with FMO1, it would not affect the overall enantioselective formation of DMANO in human liver microsomes. Enantioselectivities in the formation of MA and DMANO in human liver microsomes were consistent with those of CYP2D6 and FMO1, respectively.

Catalytic Asymmetric Synthesis of Spirocyclic Azlactones by a Double Michael‐Addition Approach

Spirocyclic azlactones are shown to be useful precursors of cyclic quaternary amino acids, such as the constrained cyclohexane analogues of phenylalanine. These compounds are of interest as building blocks for the synthesis of artificial peptide analogues with controlled folds in the peptide backbone. They were prepared in the present study by a step- and atom-economic catalytic asymmetric tandem approach, requiring two steps starting from N-benzoyl glycine and divinylketones. The key of this protocol is the enantioselective formation of the azlactone spirocycles, which involves a PdII-catalyzed double 1,4-addition of an in situ generated azlactone intermediate to the dienone (a formal [5+1] cycloaddition). As the catalyst, a planar chiral ferrocene bispalladacycle was used. Mechanistic studies suggest a monometallic reaction pathway. Although the diastereoselectivity was found to be moderate, the enantioselectivity is usually high for the formation of the azlactone spirocycles, which contain up to three contiguous stereocenters. Spectroscopic studies have shown that the spirocycles often prefer a twist over a chair conformation of the cyclohexanone moiety.

Total Synthesis of Nominal Gobienine A

The lichen-derived glycoconjugate gobienine A is structurally more complex than most glycolipids isolated from higher plants by virtue of the all-cis substituted γ-lactone substructure embedded into its macrocyclic frame. A concise entry into this very epimerization-prone and hence challenging structural motif is presented, which relies on an enantioselective cyanohydrin formation, an intramolecular Blaise reaction, a palladium-catalyzed alkoxycarbonylation, and a diastereoselective hydrogenation of the tetrasubstituted alkene in the resulting butenolide. This strategy, in combination with ring-closing olefin metathesis for the formation of the macrocyclic perimeter, allowed the proposed structure of gobienine A (1) to be formed in high overall yield. The recorded spectral data show that the structure originally attributed to gobienine A is incorrect and that it is not the epimerization-prone ester site on the butanolide ring that is the locus of misassignment; rather, the discrepancy must be more profound.

ChemInform Abstract: Enantioselective Formation of Substituted 3,4‐Dihydrocoumarins by a Multicatalytic One‐Pot Process.

ChemInform Abstract: Enantioselective Formation of Substituted 3,4‐Dihydrocoumarins by a Multicatalytic One‐Pot Process.

ChemInform Abstract: Asymmetric Autocatalysis Triggered by Chiral Crystals Formed from Achiral Compounds and Chiral Isotopomers

AbstractReview: 77 refs.

Enantioselective Formal Aza-Diels–Alder Reactions of Enones with Cyclic Imines Catalyzed by Primary Aminothioureas

A highly enantio- and diastereoselective synthesis of indolo- and benzoquinolizidine compounds has been developed through the formal aza-Diels-Alder reaction of enones with cyclic imines. This transformation is catalyzed by a new bifunctional primary aminothiourea that achieves simultaneous activation of both the enone and imine reaction components.

ChemInform Abstract: Pentanidium‐Catalyzed Enantioselective α‐Hydroxylation of Oxindoles Using Molecular Oxygen.

AbstractHydroperoxide oxindoles are formed as by‐products.

Synergistic Lewis base and anion-binding catalysis for the enantioselective vinylogous addition of deconjugated butenolides to allenoates

An enantioselective vinylogous umpolung addition of deconjugated butenolides to allenoates has been developed for the first time with the help of synergistic combination of an achiral phosphine and a chiral squaramide, and represents the first example of a catalytic enantioselective Cγ-Cγ bond formation between two different carbonyl partners.